New genetic engineering strategy makes artificial DNA invisible

Bacteria are everywhere. They live in the soil and in the water, on our skin and in our body. Some are pathogenic, which means that they cause illness or infection. To design effective treatments for pathogens, researchers need to know which genes are responsible for pathogenicity.

Scientists can identify pathogenic genes through genetic engineering. This involves the addition of DNA of human origin into a bacterial cell. However, the problem is that bacteria have developed complex defense systems to protect against foreign intruders, especially foreign DNA. Current approaches to genetic engineering often conceal human DNA in a bacterial DNA to counteract these defenses, but the process requires very specific modifications, is expensive and time consuming.

In an article published recently in the Proceedings of the National Academy of Sciences Diary, Dr. Christopher Johnston and colleagues at the Forsyth Institute describe a new technique for genetically manipulating bacteria by making artificial DNA invisible to the defenses of the bacteria. In theory, the method can be applied to almost all types of bacteria.

Johnston is a researcher in the Division of Vaccines and Infectious Diseases at the Fred Hutchinson Cancer Research Center and lead author of the article. He said that when a bacterial cell detects that it has been penetrated by foreign DNA, it quickly destroys the intruder. Bacteria live under the constant threat of virus attacks, so they have developed incredibly effective defenses against these threats.

The problem, Johnston explained, is that when scientists want to insert human DNA into bacteria, they come up against the same defense systems that protect bacteria against viruses.

To overcome this barrier, scientists add specific modifications to conceal human DNA and cause the bacteria to think that the intruder is part of its own DNA. This approach works sometimes but can take a lot of time and resources.

Johnston's strategy is different. Instead of adding a disguise to the DNA made by humans, it removes a specific component of its genetic sequence called pattern. The bacterial defense system needs this pattern to recognize foreign DNA and organize an effective counter-attack. By removing the motif, the DNA created by the human becomes essentially invisible to the defense system of the bacteria.

"Imagine a bacteria resembling an enemy submarine in a dry dock and a genetic tool made by the man as a soldier who must penetrate inside the submarine to carry out a specific task The current approaches would be like disguising the spy as an enemy soldier, have them approach each door, allowing the guards to check their identity information and, if all goes well, they will enter it. " said Johnston. "Our approach is to make this soldier invisible and to make him sneak through the doors, avoiding the guards."

This new method requires less time and resources than current techniques. In the study, Johnston used the bacteria Staphylococcus aureus as a model, but the underlying strategy he developed can be used to bypass these major defense systems that exist in 80 to 90% of the bacteria known to date .

This new genetic engineering tool opens up possibilities for research on bacteria that have not been studied well before. Because scientists have limited time and resources, they tend to work with already introduced bacteria, Johnston said. With this new tool, the DNA has been solved and researchers can use this method to create more clinically relevant bacteria.

"Bacteria are the vectors of our planet," said Dr. Gary Borisy, principal investigator at the Forsyth Institute and co-author of the paper. "The engineering capacity of bacteria has profound implications for medicine, agriculture, the chemical industry and the environment."